NICEVIVA
MONOGRAPH SPEC LATEST 2026

Perilla frutescens

TRADITIONAL ASIAN · Evidence Monograph

Perilla frutescens is an evidence-graded traditional asian monograph evaluated across 23 peer-reviewed PubMed studies (0 meta-analyses, 3 systematic reviews, and 5 randomized controlled trials, encompassing n = 175 cumulative participants). Current clinical evidence is rated GRADE Moderate (3.0 / 4.0) for targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support.

Evidence Grade (GRADE) Moderate (3.0 / 4.0)
Indexed PubMed Studies 23 Studies
Meta-Analyses · Reviews 0 Meta · 3 Systematic Reviews
Randomized Trials (RCT) 5 RCTs (7 Double-Blind)
Cumulative Participants n = 175
Reported Trial Dosages 500 mg/day · 1080 mg · 0.88 g
Trial Duration Range 12 weeks · 8 weeks · 12 months
Reading Time ~12 min
RECOMMENDED FOR Clinical Indication

Evidence Supports Supplementation When:

  1. 01 Individuals seeking evidence-backed support for targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support (supported by 23 indexed PubMed studies, GRADE Moderate).
  2. 02 Adults matching clinical trial dosing protocols (500 mg/day · 1080 mg · 0.88 g) over a structured 12 weeks evaluation window.
  3. 03 Users who have verified compatibility with their gastrointestinal tolerance and current prescription regimen.
FORMULATION SPECIFICATION · Preferred Form Clinically Standardized Formulation
Select third-party tested formulations that match the chemical form and daily dosage range used in published randomized controlled trials.
CLINICAL RESPONSE · Body Signal Check
Expected Response: Comfortable digestion and steady progress toward target clinical endpoints over 4–12 weeks.
Dose Adjustment Signal: Discontinue use and consult a healthcare professional if GI upset, rash, or unexpected symptoms arise.
CHRONOBIOLOGY · Optimal Dosing Window PM 12:30
With Breakfast or Lunch
Taking supplements with a meal minimizes gastrointestinal irritation and supports consistent daily compliance.
Primary Clinical Endpoints & Physiological Biomarkers Studied Based on Indexed PubMed Trials
antioxidant (PubMed clinical endpoint)
brain (PubMed clinical endpoint)
bone (PubMed clinical endpoint)
alopecia (PubMed clinical endpoint)
hair (PubMed clinical endpoint)
01

What Is Perilla frutescens & Why Does Form Matter?

Perilla frutescens is classified under TRADITIONAL ASIAN and has been investigated across 23 peer-reviewed PubMed publications for its role in targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support.

In clinical nutrition, physiological efficacy depends heavily on the specific chemical salt, chelate, or standardized extract used, as well as adherence to trial-validated dosing (500 mg/day, 1080 mg, 0.88 g).

02

Who Benefits Most & Common Depletion Factors

Suboptimal status or increased physiological demand for Perilla frutescens frequently arises from restrictive dietary patterns, age-related declines in gastrointestinal absorption, chronic metabolic stress, or medication-induced nutrient depletion.

Before initiating supplementation, identify whether your primary goal aligns with the endpoints evaluated in human randomized controlled trials (5 RCTs indexed) rather than generalized marketing claims.

03

Physiological Mechanism of Action

Within human physiology, Perilla frutescens acts on pathways governing targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support. Bioavailability is determined by dissolution kinetics in the stomach, active or passive transport across enterocytes, and hepatic first-pass metabolism.

Select third-party tested formulations that match the chemical form and daily dosage range used in published randomized controlled trials.

04

PubMed Clinical Evidence & GRADE Evaluation

NICEVIVA assigns Perilla frutescens an overall evidence rating of GRADE Moderate (3.0 / 4.0) based on 23 PubMed studies: 0 meta-analyses, 3 systematic reviews, and 5 randomized controlled trials (7 double-blind, n = 175 total participants).

Representative peer-reviewed findings include: • PMID:41901135 (2026) — "Efficacy and Safety of Standardized Ethanol Extract of Purple Perilla (Perilla frutescens Britton var. acuta Kudo) Leaves in Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial." (Conclusions: Twelve-week administration of PE significantly improved cognitive outcomes without safety concerns, suggesting its potential as a standardized botanical ingredient for supporting cognitive function in individuals with early cognitive impairment.) • PMID:39440465 (2025) — "Immunomodulatory effects of supercritical CO(2) extracted oils from Portulaca oleracea and Perilla frutescens (PPCE) in healthy individuals: a randomized double-blind clinical trial." (However, there were no significant differences between the two groups in the cytokines IL-6 and TNF-α.) • PMID:36637040 (2023) — "Perilla seed oil improves bone health by inhibiting bone resorption in healthy Japanese adults: A 12-month, randomized, double-blind, placebo-controlled trial." (These results suggest that long-term PO intake may improve age-related BMD decline by suppressing bone resorption and increasing LNA levels.)

05

Formulation Selection, Dosing & Chronobiology

Recommended Formulation: Clinically Standardized Formulation. Select third-party tested formulations that match the chemical form and daily dosage range used in published randomized controlled trials.

Clinical Trial Dosing & Timing: Published studies most commonly utilize 500 mg/day · 1080 mg · 0.88 g · 1.12 g over 12 weeks · 8 weeks · 12 months · 25 days. Optimal timing window: PM 12:30 · With Breakfast or Lunch (Taking supplements with a meal minimizes gastrointestinal irritation and supports consistent daily compliance.).

06

Body Response Monitoring & Dose Adjustment

Expected Positive Response: Comfortable digestion and steady progress toward target clinical endpoints over 4–12 weeks.

Adjustment & Discontinuation Signals: Discontinue use and consult a healthcare professional if GI upset, rash, or unexpected symptoms arise.

07

Prescription Drug Interactions & Contraindications

No major high-risk prescription contraindications are flagged in the primary index for Perilla frutescens, but divalent minerals, fat-soluble compounds, and botanical extracts can still alter absorption or CYP450 metabolism of concurrent medications.

Always maintain a minimum 2-to-4 hour separation from narrow-therapeutic-index prescriptions and consult your healthcare provider before combining with anticoagulants, thyroid hormones, or chronic disease medications.

08

4 Essential Safety Rules Before & After Dosing

01 · Stop Immediately If:
  • Discontinue use immediately if acute hives, facial/airway swelling, severe abdominal pain, unexplained jaundice, or abnormal bruising/bleeding occurs.
  • Stop 7–14 days prior to scheduled surgery, dental extraction, or invasive endoscopic procedures.
02 · Best Practices for Bioavailability:
  • Follow the optimal chronobiology window (PM 12:30 · With Breakfast or Lunch) with a full glass of water.
  • Stay within clinically studied daily dosages (500 mg/day · 1080 mg · 0.88 g) and re-evaluate efficacy after 12 weeks.
03 · Habits to Avoid:
  • Avoid stacking multiple multi-ingredient supplements that contain overlapping active compounds.
  • Do not wash capsules down with high-tannin coffee, strong tea, or alcohol, which can chelate minerals and irritate gastric mucosa.
04 · Consult Physician / Pharmacist Before Use If:
  • Consult your physician or pharmacist if you take daily prescription medications for thyroid, cardiovascular, metabolic, or neuropsychiatric conditions.
  • Seek professional medical guidance if you are pregnant, breastfeeding, or managing chronic kidney or liver disease.
09 · PUBMED CLINICAL STUDIES

Indexed PubMed Clinical Studies & Abstracts (23 Studies) · 5 Quantitative Analyses

01
RANDOMIZED TRIAL (RCT) Nutrients (2026) PMID: 41901135 ↗
Efficacy and Safety of Standardized Ethanol Extract of Purple Perilla (Perilla frutescens Britton var. acuta Kudo) Leaves in Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.
Clinical Trial Synthesis 2026 Randomized Controlled Trial (RCT) published in Nutrients involving n = 50 participants. Key conclusion: Conclusions: Twelve-week administration of PE significantly improved cognitive outcomes without safety concerns, suggesting its potential as a standardized botanical ingredient for supporting cognitive function in individuals with early cognitive impairment.
View Original PubMed Abstract ↓

Objectives: This randomized, double-blind, placebo-controlled 12-week clinical trial evaluated the efficacy and safety of a standardized ethanol extract of purple perilla leaves (Perilla frutescens Britton var. acuta Kudo; PE) in adults with cognitive impairment. Methods: Subjects who met the inclusion criteria were randomly assigned in a 1:1 ratio to one of two groups and received PE (n = 50, 500 mg/day) or placebo (n = 50) for 12 weeks. The primary efficacy outcomes included cognitive function, which was assessed by the Korean mini-mental status examination-2 (K-MMSE-2) and the Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog), and plasma amyloid β (Aβ) and brain-derived neurotrophic factor (BDNF) levels, which were measured as secondary biochemical markers. The safety biomarkers were also assessed before and after the intervention. Results: After 12 weeks of intervention, the K-MMSE-2 total score, the K-MMSE-2 subdomain scores (attention and calculation and language), the ADAS-Cog total score, and the ADAS-Cog subscale scores (word recall, commands, delayed word recall, naming, word recognition, and recall instructions) showed statistically significant between-group improvements compared with the placebo group. Improvements were observed in both groups, whereas the magnitude of cognitive enhancement was greater in the PE group, indicating an effect beyond placebo-related responses. No statistically significant between-group differences were observed in plasma Aβ or BDNF levels. The safety evaluation found no clinically significant changes. Conclusions: Twelve-week administration of PE significantly improved cognitive outcomes without safety concerns, suggesting its potential as a standardized botanical ingredient for supporting cognitive function in individuals with early cognitive impairment.

02
RANDOMIZED TRIAL (RCT) Food & function (2025) PMID: 39440465 ↗
Immunomodulatory effects of supercritical CO(2) extracted oils from Portulaca oleracea and Perilla frutescens (PPCE) in healthy individuals: a randomized double-blind clinical trial.
Clinical Trial Synthesis 2025 Randomized Controlled Trial (RCT) published in Food & function; statistical significance reported at p = 0.05. Key conclusion: However, there were no significant differences between the two groups in the cytokines IL-6 and TNF-α.
View Original PubMed Abstract ↓

The human immune system plays a crucial role in defending the body against various infections, viruses, and external substances, contributing to overall well-being. However, an imbalance in the immune system can lead to increased susceptibility to infections, impacting overall health. Preclinical investigations suggest the potential application of Portulaca oleracea L. and Perilla frutescens var. japonica Hara seed complex extract (PPCE) as a potent biological response modifier in terms of immunity. However, the safety and efficacy of PPCE in boosting immune function have not been investigated clinically. The present study aims to evaluate the safety and efficacy of PPCE on the immune system in healthy adults. An 8-week randomized, double-blinded, placebo-controlled cross-over clinical trial was adopted for the study. Study participants were administered either 1080 mg day-1 of a PPCE supplement or a placebo. The study assessed the Natural Killer (NK) cell activity as the primary outcome measure. Serum concentrations of cytokines (IL-6, IL-12, IFN-γ, TNF-α) and a questionnaire-based assessment of upper airway infection were the secondary outcomes. At the end of the 8 weeks, NK cell activity significantly improved in the PPCE group compared to the placebo group (p < 0.05). Similarly, the concentrations of IFN-γ and IL-12 significantly increased (p < 0.05). However, there were no significant differences between the two groups in the cytokines IL-6 and TNF-α. Additionally, no adverse effects were observed during the trial. These findings suggest that PPCE supplementation is safe and potentially benefits immune stimulation by enhancing NK cell activity and inducing the production of Th-1 type cell-stimulating cytokines like IL-12 in healthy individuals.

03
RANDOMIZED TRIAL (RCT) Phytotherapy research (2023) PMID: 36637040 ↗
Perilla seed oil improves bone health by inhibiting bone resorption in healthy Japanese adults: A 12-month, randomized, double-blind, placebo-controlled trial.
Clinical Trial Synthesis 2023 Randomized Controlled Trial (RCT) published in Phytotherapy research involving n = 25 participants. Key conclusion: These results suggest that long-term PO intake may improve age-related BMD decline by suppressing bone resorption and increasing LNA levels.
View Original PubMed Abstract ↓

Accumulating evidence suggests the beneficial effect of omega-3 polyunsaturated fatty acids (PUFAs) on bone mineral density (BMD). However, the effects of perilla (Perilla frutescens) seed oil (PO), a rich source of α-linoleic acid (LNA), on human bone have not yet been elucidated. This randomized, double-blind, placebo-controlled trial investigated the effects of long-term PO intake on bone health in Japanese adults. After screening for eligibility, 52 participants (mean age 54.2 ± 6.4 years) were randomly assigned to placebo (n = 25) and PO (n = 27) groups, which received 7.0 ml of olive oil and PO daily, respectively. At baseline and 12-month, quantitative ultrasound of the right calcaneus was measured with an ultrasound bone densitometer and percentage of the Young Adult Mean (%YAM) was calculated. Serum levels of tartrate-resistant acid phosphatase 5b (TRACP-5b), and bone alkaline phosphatase (BALP) were evaluated. In addition, PUFA levels in the erythrocyte plasma membrane (RBC-PM), serum biological antioxidant potential (BAP), and diacron reactive oxygen metabolites (d-ROM) were evaluated. Compared with the placebo group, %YAM levels increased and serum TRACP-5b levels decreased significantly in the PO group at 12-month, while serum BALP levels remained unchanged. Moreover, RBC-PM LNA levels and BAP/d-ROM ratios increased significantly in the PO compared with the placebo group. These results suggest that long-term PO intake may improve age-related BMD decline by suppressing bone resorption and increasing LNA levels. © 2023 John Wiley & Sons Ltd.

04
CLINICAL STUDY Food & function (2022) PMID: 35722977 ↗
Perilla frutescens seed oil combined with Anredera cordifolia leaf powder attenuates age-related cognitive decline by reducing serum triglyceride and glucose levels in healthy elderly Japanese individuals: a possible supplement for brain health.
Clinical Trial Synthesis 2022 Randomized Controlled Trial (RCT) published in Food & function. Key conclusion: The effects of combined supplementation on cognitive function also showed a significant negative correlation with serum CML levels after 12 months of intervention.
View Original PubMed Abstract ↓

We have shown that Anredera cordifolia extract improves learning and memory in a senescence-accelerated mouse model, and that α-linolenic acid (ALA)-rich Perilla frutescens seed oil (PO) improves brain function in healthy Japanese adults and elderly individuals. Herein, we present a 12-month, randomised, double-blind, parallel-armed intervention trial examining the effects of PO supplementation alone or in combination with A. cordifolia leaf powder on brain function in healthy elderly Japanese individuals. Participants were randomly divided into two groups: the PO group received 1.47 mL PO (0.88 g ALA) daily via soft gelatine capsules, and the POAC group received 1.47 mL PO and 1.12 g A. cordifolia leaf powder (1.46 mg vitexin and 1.12 mg adenosine) daily. After 12 months of intervention, the POAC group showed generally higher cognitive index scores than the PO group. The beneficial effects of combined supplementation on cognitive function were associated with increased ALA and eicosapentaenoic acid levels in red blood cell plasma membranes, increased serum biological antioxidant potential, and decreased serum triglyceride, glucose, and N-(epsilon)-carboxymethyl-lysine (CML), an advanced glycation end-product and biochemical marker of oxidative stress levels. The effects of combined supplementation on cognitive function also showed a significant negative correlation with serum CML levels after 12 months of intervention. Our findings suggest that combined long-term supplementation with PO and A. cordifolia more effectively ameliorates age-related cognitive decline than PO alone. These findings may serve as a basis for the development of new supplements for brain health. Clinical Trial Registry, UMIN000040863.

05
RANDOMIZED TRIAL (RCT) Nutrients (2022) PMID: 35565689 ↗
Perilla Fruit Oil-Fortified Soybean Milk Intake Alters Levels of Serum Triglycerides and Antioxidant Status, and Influences Phagocytotic Activity among Healthy Subjects: A Randomized Placebo-Controlled Trial.
Clinical Trial Synthesis 2022 Randomized Controlled Trial (RCT) published in Nutrients involving n = 100 participants; statistical significance reported at p = 0.05. Key conclusion: We are now better positioned to recommend the consumption of PFO-SM drink for the reduction of many chronic diseases.
View Original PubMed Abstract ↓

This study aimed to develop perilla fruit oil (PFO)-fortified soybean milk (PFO-SM), identify its sensory acceptability, and evaluate its health outcomes. Our PFO-SM product was pasteurized, analyzed for its nutritional value, and had its acceptability assessed by an experienced and trained descriptive panel (n = 100) based on a relevant set of sensory attributes. A randomized clinical trial was conducted involving healthy subjects who were assigned to consume deionized water (DI), SM, PFO-SM, or black sesame-soybean milk (BS-SM) (n = 48 each, 180 mL/serving) daily for 30 d. Accordingly, health indices and analyzed blood biomarkers were recorded. Consequently, 1% PFO-SM (1.26 mg ALA rich) was generally associated with very high scores for overall acceptance, color, flavor, odor, taste, texture, and sweetness. We observed that PFO-SM lowered levels of serum triglycerides and erythrocyte reactive oxygen species, but increased phagocytosis and serum antioxidant activity (p < 0.05) when compared to SM and BS-SM. These findings indicate that PFO supplementation in soybean milk could enhance radical-scavenging and phagocytotic abilities in the blood of healthy persons. In this regard, it was determined to be more efficient than black sesame supplementation. We are now better positioned to recommend the consumption of PFO-SM drink for the reduction of many chronic diseases. Randomized clinical trial registration (Reference number 41389) by IRSCTN Registry.

06
CLINICAL STUDY Food & function (2022) PMID: 35171190 ↗
Perilla seed oil in combination with nobiletin-rich ponkan powder enhances cognitive function in healthy elderly Japanese individuals: a possible supplement for brain health in the elderly.
Clinical Trial Synthesis 2022 Randomized Controlled Trial (RCT) published in Food & function. Key conclusion: We demonstrate that 12-month intervention with POPP enhances serum BDNF and antioxidant potential, and may improve age-related cognitive impairment in healthy elderly people by increasing red blood cell ω-3 fatty acid levels.
View Original PubMed Abstract ↓

Perilla (Perilla frutescens) seed oil (PO), rich in α-linolenic acid (ALA), can improve cognitive function in healthy elderly Japanese people. Here, supplements containing either PO alone or PO with nobiletin-rich air-dried immature ponkan powder were examined for their effects on cognitive function in 49 healthy elderly Japanese individuals. Patients were enrolled in a 12-month randomized, double-blind, parallel-armed study. Randomized participants in the PO group received soft gelatin capsules containing 1.47 mL (0.88 g of ALA) of PO daily, and those in the PO + ponkan powder (POPP) group received soft gelatin capsules containing both 1.47 mL of PO and 1.12 g ponkan powder (2.91 mg of nobiletin) daily. At the end of intervention, the POPP group showed significantly higher cognitive index scores than the PO group. The pro-cognitive effects of POPP treatment were accompanied by increases in ALA and docosahexaenoic acid levels in red blood cell plasma membranes, serum brain-derived neurotropic factor (BDNF) levels, and biological antioxidant potential. We demonstrate that 12-month intervention with POPP enhances serum BDNF and antioxidant potential, and may improve age-related cognitive impairment in healthy elderly people by increasing red blood cell ω-3 fatty acid levels. Clinical Trial Registry, UMIN000040863.

07
CLINICAL STUDY Fitoterapia (2025) PMID: 40466875 ↗
Components, isolated from perilla leaves, synergistically alleviate the inflammation of acute lung injury via Syk/β2-integrin pathway.
Clinical Trial Synthesis 2025 Clinical Study published in Fitoterapia. Key conclusion: Thus, our study provides a method to rapidly screen anti-ALI components from PLE, and validates their synergistic compatibility ratio, which increases their druggability and application in drug combination therapy against ALI.
View Original PubMed Abstract ↓

Perilla frutescens (L.) Britton has been widely used to treat respiratory diseases. Acute lung injury (ALI) is a complex and heterogeneous disease characterized by airway inflammation, pulmonary edema and hypoxia, but still lacks effective medications in clinic. Therefore, in this study, active components from perilla leaf extract (PLE) were identified and their therapeutic efficacy and mechanisms against ALI were further investigated. Using anti-inflammation bioactivity-guided fractionation, a fraction (PLE-A) with the highest anti-inflammatory activity was obtained from PLE, in which, the main components of Rosmarinic Acid (RosA) and Scutellarin (Scu) were identified by LC-MS/MS. And then, the synergistic anti-inflammatory effects of major compounds were screened by SynergyFinder, and confirmed in vitro and in vivo. Furthermore, in vivo, PLE-A, RosA and Scu attenuated LPS-induced ALI, while the compatibility of RosA and Scu showed stronger activity than single compound, as well as in vitro suppressed LPS-induced monocyte/macrophage inflammation. Mechanically, the compatibility of RosA, Scu synergistically inhibited the expression and phosphorylation of Syk, LFA-1 and Mac-1 in vitro. Our findings demonstrated that RosA and Scu, the major compounds from PLE-A, synergistically alleviates airway inflammation of ALI potentially through inhibiting of Syk/β2-integrin pathway. Thus, our study provides a method to rapidly screen anti-ALI components from PLE, and validates their synergistic compatibility ratio, which increases their druggability and application in drug combination therapy against ALI.

08
CLINICAL STUDY Oncotarget (2015) PMID: 26513295 ↗
Evaluation of pentacyclic triterpenes found in Perilla frutescens for inhibition of skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate.
Clinical Trial Synthesis 2015 Clinical Study published in Oncotarget. Key conclusion: The greater ability of 3-epiCA and MA to inhibit skin tumor promotion was associated with greater reduction of Cox-2 and Twist1 proteins and inhibition of activation (i.e., phosphorylation) of IGF-1R, STAT3 and Src.
View Original PubMed Abstract ↓

A series of pentacyclic tritperpenes found in Perilla frutescens (P. frutescens), including ursolic acid (UA), oleanolic acid (OA), corosolic acid (CA), 3-epi-corosolic acid (3-epiCA), maslinic acid (MA), and 3-epi-maslinic acid (3-epiMA) were evaluated for their effects on epidermal cell signaling, proliferation, and skin inflammation in relation to their ability to inhibit skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) and compared to UA as the prototype compound. All compounds were given topically 30 min prior to each TPA application and significantly inhibited skin tumor promotion. 3-epiCA and MA were significantly more effective than UA at inhibiting tumor development. All of these compounds significantly inhibited epidermal proliferation induced by TPA, however, CA, 3-epiCA and MA were more effective than UA. All compounds also reduced skin inflammation (assessed by infiltration of mast cells and T-cells) and inflammatory gene expression induced by TPA, however, 3-epiCA and MA were again more effective than UA. The greater ability of 3-epiCA and MA to inhibit skin tumor promotion was associated with greater reduction of Cox-2 and Twist1 proteins and inhibition of activation (i.e., phosphorylation) of IGF-1R, STAT3 and Src. Further study of these compounds, especially 3-epiCA and MA, for chemopreventive activity in other cancer model systems is warranted.

09
CLINICAL STUDY Hong Kong medical journal = Xianggang yi xue za zhi (2012) PMID: 23249852 ↗
Interaction between oseltamivir and herbal medicines used for treating avian influenza.
Clinical Trial Synthesis 2012 Clinical Study published in Hong Kong medical journal = Xianggang yi xue za zhi. Key conclusion: [email protected] PMID: 23249852 [Indexed for MEDLINE]
View Original PubMed Abstract ↓

83. Hong Kong Med J. 2012 Dec;18 Suppl 6:34-6. Interaction between oseltamivir and herbal medicines used for treating avian influenza. Yang MS(1), Law FC, Wong RN, Mak NK, Wei XY. Author information: (1)Department of Biology, Hong Kong Baptist University, Hong Kong SAR, China. [email protected] PMID: 23249852 [Indexed for MEDLINE]

10
RANDOMIZED TRIAL (RCT) Frontiers in pharmacology (2023) PMID: 36998613 ↗
Efficacy of Perilla frutescens (L.) Britton var. frutescens extract on mild knee joint pain: A randomized controlled trial.
Clinical Trial Synthesis 2023 Randomized Controlled Trial (RCT) published in Frontiers in pharmacology; statistical significance reported at p = 0.001. Key conclusion: Conclusion: Eight weeks of PFE intake was more effective than placebo in reducing knee joint pain and improving knee joint function in sub-healthy people with mild knee joint pain, and there were no major safety concerns.
View Original PubMed Abstract ↓

Objectives: This study aimed to evaluate the clinical efficacy and safety of PE extracts developed for the purpose of relieving pain and improving knee joint function on semi-healthy people with mild knee joint pain. Methods: A randomized, double-blind, two-arm, single-center, placebo-controlled clinical trial was conducted. Individuals with knee joint pain and a visual analogue scale (VAS) score < 50 mm were included in the study, and participants with radiological arthritis were excluded. Participants were administered either PFE or a placebo capsule (700 mg, twice a day) orally for eight weeks. The comparisons of the changed VAS score and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) scores between the PFE and placebo groups were primary outcomes, while the five inflammation-related laboratory tests including cartilage oligomeric matrix protein, cyclooxygenase-2, neutrophil and lymphocyte ratio, high sensitive C-reactive protein, and erythrocyte sedimentation rate were secondary outcomes. Also, a safety assessment was done. Results: Eighty participants (mean age, 38.4 ± 14.0, male: female, 28:52) were enrolled; 75 completed the trial (PFE 36 and placebo 39). After eight weeks, both VAS and WOMAC scores were reduced in the PFE and placebo groups. The changed scores were significantly higher in the PFE group compared to the placebo group: 19.6 ± 10.9 vs. 6.8 ± 10.5; VAS scores (p < 0.001), and 20.5 ± 14.7 vs. 9.3 ± 16.5; total WOMAC scores (p < 0.01) including the sub-scores for pain, stiffness, and functions. No significant changes were reported in the five inflammation-related laboratory parameters. All adverse events were considered minor and unlikely to result from the intervention. Conclusion: Eight weeks of PFE intake was more effective than placebo in reducing knee joint pain and improving knee joint function in sub-healthy people with mild knee joint pain, and there were no major safety concerns. Clinical Trial Registration: https://cris.nih.go.kr/cris/search/detailSearch.do?search_lang=E&focus=reset_12&search_page=M&pageSize=10&page=undefined&seq=23101&status=5&seq_group=19745, identifier CRIS: KCT0007219.

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